The occurrence of diabetes is widespread, with approximately 8% of the population in the United States suffering from diabetes. Diabetes is a chronic disease characterized by high blood sugar due to the body's inability to effectively produce and/or use insulin. Diabetes can lead to a variety of physical complications, including but not limited to renal failure, blindness, nerve damage, heart disease, sleep apnea, and celiac disease. For example, in the United States, diabetes is the leading cause of renal failure, blindness, amputation, stroke, and heart attack. Also in the United States, diabetes is the sixth leading cause of death and has been shown to reduce the life expectancy of middle-aged adults by about five to ten years.
Over a million people in the U.S. have type I diabetes mellitus (hereinafter T1DM). T1DM results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose. According to the American Diabetes Association, the disease causes thousands of deaths every year and costs more than $20 billion annually. While all patients with T1DM require insulin for treatment, not all patients are effectively treated with insulin alone.
It has been shown that moderately controlled type 1 diabetic subjects exhibit increased rates of glucose production both at rest and during exercise, which can be accounted for by increased gluconeogenesis (see Petersen, et al., J Clin Endocrinol Metab. 2004 September; 89(9):4656-64). As such, new therapies for effectively treating T1DM in combination with insulin are needed, including methods of treating T1DM based on inhibition of gluconeogenesis.